1. Field of Invention:
This invention relates to imides and processes for their preparation and more particularly to imide intermediates for the preparation of analgesic and/or antagonist octahydrobenzofuroisoquinolines, processes for preparing the imide intermediates, and processes for preparing the octahydrobenzofuroisoquinolines from the imide intermediates.
2. Prior Art:
Octahydro-1H-benzofuro[3,2-e]isoquinoline analgesic and narcotic antagonistic compounds are disclosed in U.S. Pat. No. 4,243,688 (to Ciganek). These compounds have Formula (Ia): ##STR2## wherein: R.sup.1 is H, C.sub.1 -C.sub.10 alkyl, CH.sub.2 --R.sup.6, C.sub.2 H.sub.4 (C.sub.6 H.sub.4)R.sup.7, or (CH.sub.2).sub.n CN where n=1-3;
R.sup.2 is H, OH, C.sub.1 -C.sub.2 alkoxy, or C.sub.2 -C.sub.12 acyloxy of an alkanoic acid; PA0 R.sup.3 is separately H, OH, CH.sub.3, C.sub.1 -C.sub.2 alkoxy, C.sub.2 -C.sub.12 acyloxy of an alkanoic acid, F, or N.sub.3 ; PA0 R.sup.3 and R.sup.4 in combination are methylene or keto; PA0 R.sup.5 is H, OH, ##STR3## or OCH.sub.3 ; R.sub.6 is CH.dbd.C(R.sup.8)(R.sup.9), C.tbd.CH, C.sub.3 -C.sub.6 cycloalkyl, 2-thienyl, 2-furyl, 2-tetrahydrofuryl, methyl substituted 2-furyl, or methyl-substituted 2-tetrahydrofuryl; PA0 R.sup.7 is C.sub.1 -C.sub.3 alkyl, OCH.sub.3, Cl, Br, or F; and PA0 R.sup.8 and R.sup.9 are independently H, CH.sub.3, or Cl. PA0 R.sup.2 is H, OH, C.sub.1 -C.sub.2 alkoxy, or C.sub.2 -C.sub.12 acyloxy of an alkanoic acid; PA0 R.sup.3 is H, C.sub.1 -C.sub.8 alkyl, or C(OH)(R.sup.4)(R.sup.5); PA0 a is a single bond or a double bond; PA0 R.sup.4 is H or C.sub.1 -C.sub.8 alkyl; PA0 R.sup.5 is H, C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.8 alkenyl, C.sub.3 -C.sub.8 cycloalkyl, or (CH.sub.2).sub.m --C.sub.6 H.sub.5 in which m=0-4; PA0 R.sup.6 is CH.dbd.C(R.sup.8)(R.sup.9), C.tbd.CH, C.sub.3 -C.sub.6 cycloalkyl, phenyl, 2-thienyl, 2-furyl, 2-tetrahydrofuryl, methyl substituted 2-furyl, or methyl substituted 2-tetrahydrofuryl; PA0 R.sup.7 is H, C.sub.1 -C.sub.3 alkyl, OCH.sub.3, Cl, Br, or F; and PA0 R.sup.8 and R.sup.9 are independently H, CH.sub.3, or Cl. PA0 R.sup.1 is C.sub.1 -C.sub.10 alkyl, CH.sub.2 R.sup.6, C.sub.2 H.sub.4 (C.sub.6 H.sub.4)R.sup.7, or (CH.sub.2).sub.n CN in which n=1-3; PA0 R.sup.2 is H, OH, or C.sub.1 -C.sub.2 alkoxy; PA0 R.sup.3 is H, C.sub.1 -C.sub.8 alkyl, or COR.sup.4 ; PA0 R.sup.4 is H, C.sub.1 -C.sub.8 alkoxy, or C.sub.1 -C.sub.8 alkyl; PA0 R.sup.6 is CH.dbd.C(R.sup.8)(R.sup.9), C.tbd.CH, C.sub.3 -C.sub.6 cycloalkyl, phenyl, 2-thienyl, 2-furyl, 2-tetrahydrofuryl, methyl substituted 2-furyl, or methyl substituted 2-tetrahydrofuryl; PA0 R.sup.7 is H, C.sub.1 -C.sub.3 alkyl, OCH.sub.3, Cl, Br, or F; and PA0 R.sup.8 and R.sup.9 are independently H, CH.sub.3, or Cl. PA0 R.sup.1 is C.sub.1 -C.sub.10 alkyl, CH.sub.2 R.sup.6, C.sub.2 H.sub.4 (C.sub.6 H.sub.4)R.sup.7 or (CH.sub.2).sub.n CN in which n=1-3; PA0 R.sup.2 is H, OH, or C.sub.1 -C.sub.2 alkoxy; PA0 R.sup.3 is H, C.sub.1 -C.sub.8 alkyl, or C(OH)(R.sup.4)(R.sup.5); PA0 R.sup.4 is H, or C.sub.1 -C.sub.8 alkyl; PA0 R.sup.5 is H, C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.8 alkenyl, C.sub.3 -C.sub.8 cycloalkyl, or (CH.sub.2).sub.m --C.sub.6 H.sub.5 in which m=0-4; PA0 R.sup.6 is CH.dbd.C(R.sup.8)(R.sup.9), C.tbd.CH, C.sub.3 -C.sub.6 cycloalkyl, phenyl, 2-thienyl, 2-furyl, 2-tetrahydrofuryl, methyl substituted 2-furyl, or methyl substituted 2-tetrahydrofuryl; PA0 R.sup.7 is H, C.sub.1 -C.sub.3 alkyl, OCH.sub.3, Cl, Br, or F; and PA0 R.sup.8 and R.sup.9 are independently H, CH.sub.3, or Cl; comprising PA0 (c) optionally contacting and reacting the product of step (b)(ii) with catalytic hydrogenation in the liquid phase at a temperature in the range of about 20.degree.-100.degree. C.; and PA0 (d) contacting and reacting the product of step (b) or step (c) with a complex metal hydride in the liquid phase at a temperature in the range of about 25.degree.-150.degree. C.
R.sup.4 is separately H or F; PA1 (a) heating a compound of Formula (IX) at a temperature in the range of about 50.degree.-300.degree. C. for a time sufficient to obtain substantial Diels-Alder reaction; PA1 (b) contacting and reacting the product of step (a) according to one of the following two steps: PA1 (i) with catalytic hydrogenation in the liquid phase at a temperature in the range of about 20.degree.-100.degree. C. PA1 (ii) with an olefin capable of introducing R.sup.3 =C.sub.1 -C.sub.8 alkyl or COR.sup.4 ;
Utility, dosage formulations, and preferred compounds are disclosed in this patent, as is a process for preparing the compounds. In particular, lactams of Formula (III) are disclosed as intermediates for the preparation of compounds of Formula (Ia) wherein R.sup.3, R.sup.4, and R.sup.5 are all H. In addition, compounds of Formulas (IV) and (V) are disclosed, along with processes for converting (V) to (IV) and for converting (IV) to (III).
Octahydro-4a,7-ethano- and ethenobenzofuro[3,2-e]isoquinoline analgesic and narcotic antagonistic compounds are disclosed in U.S. Pat. No. 4,477,456 (to Ciganek). These compounds have Formula (IIa): ##STR4## wherein: R.sup.1 is H, C.sub.1 -C.sub.10 alkyl, CH.sub.2 --R.sup.6, C.sub.2 H.sub.4 (C.sub.6 H.sub.4)R.sup.7, or (CH.sub.2).sub.n CN, in which n=1-3;
Utility, dosage formulations, and preferred compounds are disclosed in this patent, as is a process for preparing the compounds. In particular, lactams of Formula (VI) below are disclosed as intermediates for the preparation of compounds of Formula (IIa). Compounds of Formula (VI) are prepared from compounds of Formula (IV), disclosed in U.S. Pat. No. 4,243,668. ##STR5##